It is well known that certain derivatives of glycyrrhetinic acid, such as the disodium salt of the hemisuccinate of glycyrrhetinic acid, have an excellent anti-inflammatory action and are useful for the treatment of gastric and duodenal ulcers, as well as for the treatment of reflux oesophagitis.
Non-liquid pharmaceutical compositions are also known which comprise at least one hydrophilic colloid and the disodium salt of the hemisuccinate of glycyrrhetinic acid. These compositions adhere well to moist mucous membranes and have been found to be useful for the treatment of ulcerations of the oral cavity. However, the use of these compositions is restricted to cases in which the degree of ulceration is limited and in which the ulcerations are readily accessible. Furthermore, these compositions cannot be used topically in conventional water-containing pharmaceutical cream compositions because the glycyrrhetinic acid derivatives are of very limited stability in the presence of water and are hydrolysed to give the substantially less active glycyrrhetinic acid.
Glycyrrhetinic acid derivatives have been found to have outstandingly useful properties for treating viral infections. In our earlier British Patent Application No. 82.01121, there is described and claimed a water-soluble or water-dispersible particulate and preferably granulated pharmaceutical composition comprising, per one part by weight of glycyrrhetinic acid and/or of a glycyrrhetinic acid derivative, as hereinafter defined, 10 to 100 and preferably 30 to 80 parts by weight of lactose and/or sorbitol, 10 to 50 and preferably 15 to 25 parts by weight of at least one buffer selected from sodium citrate, potassium citrate, sodium tartrate, potassium tartrate, sodium malate and potassium malate and 0.1 to 10 parts and preferably 0.3 to 1 part by weight of disodium edetate and optionally comprising a colouring and/or flavouring material.
Many inflammatory conditions and viral infections are of a topical nature, such as herpes infections of the lips and of the anal and genital regions, for example balanitis. Ideally, a pharmaceutical composition for the treatment of such conditions and infections would be in the form of a cream containing the active material. However, as mentioned hereinbefore, one of the great disadvantages of active derivatives of glycyrrhetinic acid is that they are unstable in the presence of water which precludes the use of conventional water-containing pharmaceutical cream bases.
Consequently, it is an object of the present invention to provide stabilised, water-containing pharmaceutical creams containing glycyrrhetinic acid derivatives, which creams are suitable for topical administration.
We have now found that certain inorganic, nontoxic, water-soluble salts act as outstanding stabilisers for glycyrrhetinic acid derivatives when incorporated into a water-containing pharmaceutical cream base, the hydrolysis to glycyrrhetinic acid being almost completely suppressed.